肺癌的发病率及死亡率均居于肿瘤的首位，且呈逐年上升的趋势，其中复发和转移是导致肺癌治疗失败主要原因。随着肿瘤干细胞的研究深入，认为在肿瘤的侵袭、转移中，肿瘤干细胞发挥了重要的作用。失巢凋亡作为特殊的细胞程序化死亡形式，也是肿瘤侵袭、转移中关键的步骤之一。本课题组的前期研究发现，肺癌细胞系H460可发生失巢凋亡，但CD133阳性的肺癌干细胞具有明显的抗失巢凋亡特性。失巢凋亡发生是一个非常复杂的过程，涉及多个信号转导通路，迄今为止，肿瘤干细胞发生抗失巢凋亡的具体机制尚不清楚。本课题拟在前期工作基础上，综合利用差异磷酸化蛋白质组学、相关信号转导通路的激动剂或抑制剂、基因干涉技术以及体内荷瘤动物模型等探索与肺癌干细胞抗失巢凋亡相关的信号转导通路或关键信号转导分子，为进一步阐明肿瘤干细胞抗失巢凋亡的分子机制奠定基础，为肺癌的临床治疗提供新的策略，为肿瘤转移和复发的相关研究提供新的思路。

Lung cancer is the leading cause of cancer death worldwide. Lung cancer accounts for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths in 2008. The general prognosis of lung cancer is poor, with overall survival rates of less than 15% at five years. More and more evidence show that the increased mortality are mainly due to cancer recurrence and metastasis, and in which cancer stem cells play a key role. Anoikis as a special kind of programmed cell death is an important step in cell migration and metastasis. There is therefore an urgent need for clarify whether and how cancer stem cells contribute to tumor migration and metastasis by undergoing anti-anoikis. In our earlier studies, lung cancer stem cells (CSCs) were isolated from H460 deriving drug surviving cells according to the literature, then we have found general lung cancer cell line H460 underwent anoikis, however CD133 positive lung cancer stem cells show the obvious anti-anoikis. Anoikis is a complex process which involved several signal transduction pathway, otherwise the molecular mechanisms is still unclear. In this proposal, we will employ difference assay of phosphoproteomics, activator and inhibitor of signaling pathway, siRNA transfection and in vivo tumor-bearing animal models in analysis of key signaling molecules which contribute to anti-anoikis of lung cancer stem cells, This proposal will therefore clarify the effects and mechanisms of key phosphorylated proteins and pathway in anti-anoikis, and further provide the new therapeutic strategy of lung cancer clinical trial and in treating cancer recurrence and metastasis.